Superoxide anion (02), is a product of cellular metabolism, generated due to partial reduction of molecular oxygen. As the presence of 02 can diminish the half life of nitric oxide (NO), the potential role of 02-NO interactions in the regulation of many biological events has been a major focus of many recent studies. Angiotensin II (ANG II) induces both 02 and NO production, indicating a possible role of NO-02 interaction in the pathophysiology of hypertension. Thus, the primary objectives of this project are to elucidate the interacting role of 02 and NO in the control of renal cortical and medullary circulation as well as tubular reabsorptive function. The hypothesis to be tested is that changes in intrarenal NO activity reciprocally regulate intrarenal 02 levels, which have a direct influence on renal hemodynamics and tubular function leading to alteraction in net sodium reabsorption rate. A deficiency in such regulation of NO and O2 may play a role in the development of ANG II dependent hypertension. Assessment of the interacting role of O2 and NO will be made in acute preparations in dogs as well as in chronic ANG II induced hypertensive rats. The effects of the administrations of tempol (a stable SOD mimetic) as well as a SOD inhibitor, Diethyldithiocarbamate on total and regional renal blood flows and excretory function will be assessed in the presence and absence of NO synthase inhibition. These assessments in renal regional hemodynamics will be made with the aid of single fiber laser Doppler needle flow probes in association with measurements of intrarenal NO activity using NO microelectrode and interstitial 8-isoprostanes level using microdialysis technique. It is anticipated that these experiments will provide a more complete understanding of the interactive role of 02 and NO in the regulation of renal cortical and medullary blood flows as well as excretory function both in under normal condition as well as in ANG II dependent hypertension.